PYX-201 Receives Orphan Drug Designation From the FDA in Pancreatic Cancer

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The FDA has granted an orphan drug designation to PYX-201 for the treatment of patients with pancreatic cancer.

The FDA has granted an orphan drug designation (ODD) to PYX-201 for the treatment of patients with pancreatic cancer.¹ Preliminary data from the ongoing phase 1 PYX-201-101 trial of PYX-201 in solid tumors (NCT05720117) is expected in early 2024.²

“PYX-201 has the potential to offer a new approach to targeting multiple tumor types via a multipronged mechanism of action that may benefit patients with solid tumors. We expect to see preliminary data from this study, including biomarker results and potential early signs of clinical activity, in early 2024,” Lara S. Sullivan, MD, president and chief executive officer of Pyxis Oncology, stated in a news release. “I’m proud of the work done by the Pyxis Oncology team to initiate dosing in our first clinical trial. Dosing is a significant achievement and important milestone that marks the transition of Pyxis Oncology to a clinical-stage company.”

PYX-201 is a novel antibody-drug conjugate designed to target extradomain-B (EDB) of fibronectin, a non-internalizing antigen, that is a key part of the extracellular matrix in tumors. EDB fibronectin is overexpressed in many solid tumors and has minimal expression in most normal adult tissues.

The agent is currently under study in the open-label, multicenter, PYX-201-101 dose-escalation trial, where its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy will be evaluated. To be eligible for enrollment, patients must have received a diagnosis of a relapsed or refractory solid tumor, including non–small cell lung cancer, hormone receptor–positive breast cancer, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma, soft tissue sarcoma, hepatocellular carcinoma, and kidney cancer.

For the dose-escalation portion of the study, the population will include those who have developed disease progression through standard therapy and those for whom standard-of-care therapy associated with survival benefit is unavailable or unsuitable.

In addition, patients must have an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria––with the exception of patients with bone-only metastatic breast cancer––life expectancy of at least 3 months, and archived or fresh tumor samples for screening.

The primary end points of the study include the determination of the number of patients who experience a dose-limiting toxicity and any adverse effect.³ Key secondary efficacy end points include objective response rate, duration of response, progression-free survival, disease control rate, time to response, and overall survival.

“We are always looking for potential new treatments for patients who have limited or no options available. I am particularly excited about PYX-201 because it was designed to offer several important safety and efficacy improvements compared to traditional ADCs, and we look forward to evaluating it in this phase 1 study,” Alexander Spira, MD, director of NEXT Oncology Virginia, co-director of VCS Research Institute, and director of the Thoracic and Phase I Program and clinical assistant professor at Johns Hopkins University, said.

The company’s other drug candidate, PYX-106, will also undergo evaluation in tumor-specific expansion cohorts following dose selection. Clinical sites are open and patient screening is underway for the phase 1 PYX-106-101 trial (NCT05718557). Dosing is expected to begin during the second quarter of 2023.

“The first quarter of 2023 was marked by the transition of Pyxis Oncology to a clinical-stage company as we initiated two Phase 1 trials for PYX-201 and PYX-106,” Sullivan said. “Receipt of ODD for PYX-201 in pancreatic cancer is an important achievement highlighting the need for new treatment options, and we remain focused on execution as our two clinical programs advance. We continue to anticipate preliminary data, including biomarker results and early signs of potential clinical activity, from both trials in the late-2023 to early-2024 timeframe.”